The goal of this research is to better understand the role of insulin receptors in insulin action, focusing on insulin receptors on human red blood cells and circulating monocytes. We will study insulin receptors by standard hormone binding techniques, but will also assess receptor structure and function through the use of immunologic probes and measurement of post-receptor events. We will characterize normal receptors in this manner, and will also study the insulin receptor in a variety of disease states in which insulin is impaired, such as obesity, maturity onset diabetes, and several unusual syndromes of extreme insulin resistance. The role of the membrane sodium pump, or Na ion plus K ion-ATPase, in the generation of obesity will also be explored through direct studies in mice and men.